Immune microenvironment plays crucial roles in functional homeostasis and remodelling of tissues, especially in a diseased state. So far, various approaches and biomaterials have been exploited to control the immune status through delivering of anti-inflammatory drugs, scaffolds, cell-based therapeutics and medical devices. Here, we present different formats of immunomodulation factors based on tissue-mimicking bio-scaffolds, electrical stimulation and controlled drug delivery systems. In addition, intracellular conditions are also crucial in determining cellular activities and their immune homeostasis. We aimed to modulate intracellular microenvironment through metabolic reprogramming of cells to induce functional enhancement and immunomodulation. In conclusion, we present tissue-engineered technologies modulating immune responses to achieve enhanced regenerative therapies.